Ozden Piskin

Prognostic significance of immunohistochemical classification of diffuse large B-cell lymphoma

Abstract Aim: To evaluate the clinical significance of immunoperoxidase staining for CD10, bcl-6, mum-1 and bcl-2 to subdivide DLBCL into prognostic subgroups, we analysed 50 DLBCL cases using immunohistochemical methods. Methods and results: Fifty DLBCL patients were evaluated retrospectively. The expression of CD10 was associated with better OS (p=0·04) whereas expression of mum-1 was associated with worse OS (p=0·009). There were no significance of OS in case of expression of bcl-6 (p=0·05) and bcl-2 (p=0·3). They were subclassified using CD10, mum-1, bcl-6 as germinal center B-cell like (GCB) lymphoma (30%) and non-GCB lymphoma (70%). The OS and EFS (event free survival) were longer in GCB group (p=0·002) and 5-year OS for GCB group was 92% compared with only 44% for the non-GCB group (p=0·02). The OS of the GCB group also was longer compared to that of the non-GCB group in low IPI subgroup (p=0·01). Conclusion: The existance of survival differences between GCB a non-GCB group also in the patients with low IPI score, showed the importance of prognostic classification in the risk-adaptive treatment approaches. The classification as GCB and non-GCB based immunostains may enable to define more accurate prognostic groups in DLBCL.

Gingival involvement in a patient with CD56+ chronic myelomonocytic leukemia

Leukemic infiltration of the gingiva is most commonly reported to be associated with monocytic subtypes of acute myeloblastic leukemia (AML) but rarely with myelodysplastic syndromes (MDS). Here we report a case of CD56 +  chronic myelomonocytic leukemia (CMML) who developed gingival involvement simultaneously when the leukocyte count elevated. At that time no increase in peripheral or bone marrow blasts were observed. Gingival hypertrophy regressed with the treatment of hydroxyurea. Three months later, bone marrow blast count elevated and the patient was treated with two courses of AML-like regimen and then one course of consolidation therapy. The patient is in complete hematological remission for one and a half years. Similar to other extramedullary involvements, gingival hypertrophy in CMML can be a harbinger of the disease entering a more aggressive phase requiring systemic chemotherapy.

Evaluation of circulating endothelial and platelet microparticles in men with ankylosing spondylitis.

Objective. To evaluate the profiles of endothelial microparticles (EMP) and platelet microparticles (PMP) in men with ankylosing spondylitis (AS) and healthy subjects. We also aimed to determine whether microparticles (MP) correlate with disease activity, function, and spinal mobility indices. Methods. There were 82 men with AS and 53 healthy controls. Subjects with a history of chronic diseases including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia were excluded. MP were stained with monoclonal antibodies against platelets and endothelial cells and quantified using flow cytometry. MP that were positive for both CD42a+/CD31+ and total CD42a+ were identified as PMP; and MP consisting of CD42a–/CD31+ and total CD144+ were considered EMP. Results. EMP and PMP were similar between the patient and control groups (p > 0.05). Comparison of patients with AS in the active disease state (BASDAI ≥ 4) and in the inactive state showed that EMP and PMP were not different between the groups (p > 0.05). Correlation analysis revealed no correlation with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, or Bath Ankylosing Spondylitis Metrology Index. C-reactive protein was significantly correlated with PMP and CD42a–/CD31+ EMP (p < 0.05). Comparison of patients with AS treated with anti-tumor necrosis factor (anti-TNF) drugs, subjects treated conventionally, and healthy controls revealed that PMP and CD42a–/CD31+ EMP were significantly downregulated in patients receiving biological agents. Conclusion. Circulating EMP and PMP, known to be indicators and mediators of vascular injury, were not significantly altered in men with AS who did not have classical cardiovascular risk factors. Significantly downregulated MP in patients receiving biological agents suggested that anti-TNF treatment may have a beneficial effect on vascular function in AS.

The effect of the acute submaximal exercise on thrombin activatable fibrinolysis inhibitor levels in young sedentary males.

Depending on type, duration, and intensity of the exercise, changes occur in hemostasis. In this study, we evaluated the changes in the parameters of coagulation and fibrinolytic systems that happened after the submaximal aerobic exercises by bicycle ergomater. Twelve healthy male participants whose ages were between 21 and 28 have been included. The venous samples have been drawn before the exercise as well as at the 0th, 15th, and 60th minutes after the submaximal exercise. The values of prothrombin time (PT), active partial thromboplastin time (aPTT), D-dimer, fibrinogen, plasminogen activator inhibitor 1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) have been measured. Plasminogen activator inhibitor 1 values have shown an insignificant increase after exercise (P = .328), whereas, it has decreased significantly during the resting period (P = .033) Postexercise 15th and 60th minutes TAFI values have decreased significantly comparing to basal and postexercise (0th minute) values (P = .001). Fibrinolytic system activation is observed after acute submaximal aerobic exercise of sedentary healthy participants.

The clinical, haematological and morphological profile of patients with myelodysplastic syndromes : A single institution experience from Turkey

In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p < 0.0001). In WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin <10 g/dl, neutrophil count <0.5 × 109/L, platelet count <50 × 109/L had an unfavourable prognostic impact on survival in multi-variate analysis. Our conclusions support the previous findings on the value of WHO classification for prediction of prognosis in MDS.

Increased concentration of soluble CD40 ligand in preeclampsia.

Preeclampsia has been associated with increased platelet activation detected before disease onset. Platelets are involved in hemostasis and also directly initiate an inflammatory response of the vessel wall. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis, and also as a mediator of inflammation. Platelets may release inflammatory mediators such as soluble CD40 ligand. The plasma level of soluble CD40 ligand was investigated during preeclamptic (n =20) and normal pregnancies (n = 20) to emphasize inflammatory response in preeclampsia. The mean soluble CD40 ligand levels were 1.08 ± 0.43 ng/mL in patients with preeclampsia and 0.76 ± 0.24 ng/mL in healthy pregnant women, which was statistically significant (P = .01). To clarify whether inflammation may cause inappropriate endothelial cell activation or inappropriate endothelial cell activation may start this inflammatory response, future studies are needed in a larger study population.

Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion

Background: There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. Objectives: In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. Methods: 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. Results: There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. Conclusion: Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability.

Fatal disseminated mucormycosis in a patient with mantle cell non-hodgkin's lymphoma: an autopsy case

A patient with mantle cell non-Hodgkins lymphoma presented herself with fever, nausea, right upper quadrant pain on the 7th day of R-CHOP chemotherapy. After hospitalization with the suspicion of acute cholecystitis, she received antibiotherapy with G-CSF because of emerging neutropenia at the 10th day of chemotherapy. Abdominal computed tomography revealed small infarcts in the spleen and kidneys. The ecchymotic lesion which developed on her right lateral malleolus, became bullous in the following days and treated as ecthyma gangrenosum. Although the patient was afebrile with a normal neutrophil count on the third day of antibiotherapy, she developed acute renal failure and deteriorated rapidly. The patient underwent hemodialysis but expired on the 10th day of hospitalization. Post mortem autopsy findings showed ischemic infarction and necrosis of parenchyma due to mycotic thrombosis of arteries and veins of many organs (heart, lung, diaphragm, kidneys, spleen, gut mucosa) as well as invasion of vessel walls and parenchyma by mucor. We reviewed mucormycosis in the light of this case.

Is the BFM Regimen Feasible for the Treatment of Adult Acute Lymphoblastic Leukemia? A Retrospective Analysis of the Outcomes of BFM and Hyper-CVAD Chemotherapy in Two Centers

Multiple induction regimens have been developed for adult patients with acute lymphoblastic leukemia (ALL). However, there have been no prospective randomized trials that directly compare these regimens. In this study, we wanted to evaluate the outcome of 50 adult ALL patients treated with BFM (i.e. Berlin-Frankfurt-Munster, n = 20) and hyper-CVAD (n = 30) protocols between March 2006 and October 2012. The median age was 25 years in the BFM group and 30.5 years in the hyper-CVAD group with a male/female ratio of 15:5 and 17:13, respectively. Forty-five percent of the patients in the BFM group and 30.3% in the hyper-CVAD group were <25 years old. The majority of cases were B cell in origin (80% in the BFM group and 70% in the hyper-CVAD group). Complete remission after induction therapy was achieved in 95 and 96% of the patients, respectively. The median follow-up time was 37 months. The 5-year survival rate was higher in the BFM group than in the hyper-CVAD group (59 vs. 34%). There were also no complications which could cause a delay during the hyper-CVAD regimen. Both chemotherapies were well tolerated. None of the patients died from drug-related toxicity. Only mild liver enzyme elevations were seen as toxicity in the BFM group; these did not cause any delay in therapy. The BFM regimen seems to be feasible for adult patients with ALL in terms of tolerability and efficacy, especially in young adults.

Renal and neurological response with eculizumab in a patient with transplant associated thrombotic microangiopathy after allogeneic hematopoietic progenitor cell transplantation.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenge after allogeneic hematopoietic progenitor cell transplantation, considering the diagnostic uncertainties and lack of established treatment. We report a 43-year-old male patient who was diagnosed as TA-TMA after allogeneic progenitor cell transplantation for a progressive ALK negative anaplastic large cell lymphoma and responded to eculizumab with dramatically improving neurological status and renal function. Rapid neurological and renal recovery achieved after eculizumab could support a possible relationship between complement activation and TA-TMA. Eculizumab should be a reasonable treatment approach in patients with TA-TMA after allogeneic hematopoietic progenitor cell transplantation.